Women suffer harsh consequences of gonadal toxicity and dysfunction that arise from chemotherapy and radiation therapies and developmental disorders. Treatment options are limited for resulting infertility, hormone insufficiency, and inability to go through puberty. The female ovary includes follicles, cell spheroids possessing the oocyte, and somatic cells responsible for hormone production and cycling. In humans, autotransplant of cryopreserved ovarian tissue has given patients short-term hormone cycling (<19 months) and live birth. (See, Jeruss J. N Engl J Med. 2009:360(9):902-11 and Ernst E. European Journal of Cancer. 2013; 49 (4):911-914.) Autotransplants, which are only available for patients suffering gonadotoxicity from cancer therapies, pose a risk of cancer and possess a short life span. (See, Bastings L. Hum Reprod Update. 2013; 19(5):483-506.)
Great advances in follicle culture and transplant, including live birth in mice, have been made with biomaterial strategies, most commonly hydrogel bead seeding or encapsulation. (See, Xu M. Tissue Engineering. 2006; 12(10):2739-2746.) These strategies, however, do not permit advanced design to optimize transplant function of a sustaining follicle pool. For example, in follicle culture, when follicles are seeded on top of a scaffold, the follicles observe a two-dimensional surface. As a result, the three-dimensional structure of the follicle is not supported and the stromal cells, the cells that comprise most of the follicle, leave the oocyte. Once these stromal cells leave the oocyte, the oocyte dies and there is no longer cell function. Alternatively, the follicles can be injected into and encapsulated by a hydrogel bead. In hydrogel encapsulation, the stroma cell-follicle contacts are preserved. However, in hydrogel encapsulation, only very soft (low stiffness) hydrogels can be used, otherwise the follicle will not be able to grow. Because the stiffness of the hydrogel provides a biological cue, the hydrogel beads are unable to provide an optimal material for follicle development and have been unable to restore whole organ function with cyclical endocrine production and response.